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1.
Vet Res Commun ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34671910

RESUMO

Canine parvovirus type 2 (CPV-2) is one of the most relevant pathogens associated with enteritis in dogs and is frequently reported in association with the detection of other pathogens in faeces. In this study the concomitant presence of Canine circovirus (CanineCV) and Canine adenovirus (CAdV) DNA in faecal or intestine samples of 95 dogs with parvovirus enteritis sampled in Italy (1995-2017) was investigated and the viruses identified were genetically characterised. Potential correlations with the antigenic variant of CPV-2 and with signalment data and outcome were evaluated. Twenty-eight of 95 (29.5%) CPV-2 infected dogs tested positive to other viruses: 7/28 were also positive to CanineCV, 1/28 to CAdV-1, 18/28 to CAdV-2, 1/28 to CanineCV and CAdV-2, and 1/28 to CAdV-1 and CAdV-2. The frequency of CAdV DNA detection and coinfections was significantly higher in purebred dogs compared to mixed breed ones (P = 0.002 and 0.009, respectively). The presence of coinfection was not associated with any other relevant data available, including CPV-2 variant and final outcome. The detection of CanineCV in a dog sampled in 2009 allowed to backdating its circulation in dogs. The eight CanineCV completely sequenced were phylogenetically related to the CanineCV identified in dogs, wolves and a badger from Europe, USA, Argentina and China. Nine CAdV were partially sequenced and phylogenetic analysis showed a separate branch for the oldest CAdV-2 identified (1995). From the results obtained in this study population, CanineCV and CAdV coinfections in dogs with parvoviral enteritis did not result in more severe disease.

2.
Animals (Basel) ; 11(8)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34438655

RESUMO

In this study, internal organs (tongue, intestine, and spleen) of 23 free-ranging Italian wolves (Canis lupus italicus) found dead between 2017 and 2019 were tested for Carnivore protoparvovirus 1, Canine adenovirus (CAdV), and Canine circovirus (CanineCV) using real-time PCR assays. Genetic characterisation of the identified viruses was carried out by amplification, sequencing, and analysis of the complete viral genome or informative viral genes. All the wolves tested positive for at least one of the DNA viruses screened, and 11/23 were coinfected. Carnivore protoparvoviruses were the most frequently detected viruses (21/23), followed by CanineCV (11/23) and CAdV (4/23). From the analysis of the partial VP2 gene of 13 carnivore protoparvoviruses, 12 were canine parvovirus type 2b, closely related to the strains detected in dogs and wild carnivores from Italy, and one was a feline panleukopenia-like virus. Of the four CAdV identified, two were CAdV-1 and two were CAdV-2. The complete genome of seven CanineCVs was sequenced and related to the CanineCV identified in dogs, wolves, and foxes worldwide. Close correlations emerged between the viruses identified in wolves and those circulating in domestic dogs. Further studies are needed to investigate if these pathogens may be potentially cross-transmitted between the two species.

3.
BMC Vet Res ; 17(1): 206, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090429

RESUMO

BACKGROUND: Canine parvovirus (CPV) is one of the most important pathogens of dogs. Despite vaccination, CPV infections are still ubiquitous in dogs, and the three antigenic variants 2a, 2b and 2c are variously distributed in the canine population worldwide. To date, no information is available on CPV variants circulating in some European countries. The aim of this study was to genetically characterise the CPV detected in ten dogs with clinical signs of acute gastroenteritis in Romania. The presence of Carnivore protoparvovirus 1 DNA was investigated in faecal samples using an end-point PCR targeting the complete VP2 gene and positive amplicons were sequenced and analysed. RESULTS: All ten dogs with acute gastroenteritis tested positive to Carnivore protoparvovirus 1 DNA in faecal samples. The identified viruses belonged to CPV-2c type, showed identical sequences of the VP2 gene and were characterised by distinctive amino acid residues in the deduced VP2 protein: 5-glicine (5Gly), 267-tirosine (267Tyr), 324-isoleucine (324Ile) and 370-arginine (370Arg). These distinctive amino acid residues have already been reported in CPV-2c widespread in Asia and occasionally detected in Italy and Nigeria. CONCLUSIONS: Since CPV-2c with VP2 amino acid residues 5Gly, 267Tyr, 324Ile and 370Arg were never reported before 2013, it can be assumed that this virus is progressively expanding its spread in the world dog population. This study adds new data about the presence of this new virus in Europe and underline worrying questions about its potential impact on the health of the canine population.


Assuntos
Doenças do Cão/virologia , Gastroenterite/veterinária , Infecções por Parvoviridae/veterinária , Parvovirus Canino/genética , Animais , DNA Viral/análise , Cães , Fezes/virologia , Feminino , Gastroenterite/virologia , Masculino , Infecções por Parvoviridae/virologia , Parvovirus Canino/isolamento & purificação , Reação em Cadeia da Polimerase/veterinária , Romênia
4.
Res Vet Sci ; 138: 196-200, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34171543

RESUMO

We report an outbreak of canine distemper virus (CDV) among stone martens (Martes foina) in Italy. After being rescued in Northern Italy between April and June 2018, six subjects were kept in a wildlife and exotic animal rescue center in Bologna province. Subjects have been monitored for 15 months in captivity. Within this time-lapse, two subjects died, while among the remaining four, only one showed clinical symptoms referable to distemper. Surviving subjects have been regularly tested for CDV by means of reverse transcriptase-PCR from conjunctival and oropharyngeal swabs for eleven months. The identified viruses belonged to the Wildlife-Europe CDV genetic subgroup. Neutralizing antibodies were detected at the end of the eleven months, when all subjects tested reverse transcriptase-PCR negative. Our findings confirm the circulation of the Wildlife-Europe CDV genetic subgroup (Europe 1/South America 1 lineage) within the Italian wildlife, and improve knowledge on viral infection in stone martens.


Assuntos
Anticorpos Antivirais/sangue , Surtos de Doenças/veterinária , Vírus da Cinomose Canina/imunologia , Cinomose/epidemiologia , Mustelidae , Animais , Anticorpos Neutralizantes/sangue , Cinomose/imunologia , Cinomose/virologia , Feminino , Itália/epidemiologia , Masculino
5.
Res Vet Sci ; 137: 144-149, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33975193

RESUMO

Feline Vector-Borne Diseases show increased global prevalence and some Anaplasma and Ehrlichia species may pose a risk to human health. The diagnosis of Anaplasma and Ehrlichia species infection in cats is achieved by the combined use of different methods as cytologic examination evidencing intracytoplasmic morulae, serologic tests and molecular assays. The peripheral whole blood is considered the sample of choice for Anaplasma and Ehrlichia species DNA detection in cats, but false negative results are reported leading to underestimation of infection prevalence. In order to have a more accurate assessment of the spread of feline vector-borne pathogens, the presence of Anaplasma spp. and Ehrlichia spp. DNA in 37 owner and shelter cats subjected to necropsy were prospectively investigated by testing in end-point PCR spleen, bone marrow, blood clot and hair samples. The bacteria identified were genetically characterised. Three shelter cats tested positive for A. phagocytophilum DNA in spleen (one cat) or in hair samples (two cats). None of the cats tested positive in bone marrow and blood samples. From the results obtained, it can be assumed that the use of spleen or hair samples could allow a more reliable detection of A. phagocytophilum DNA in cats with blood tested negative. In the phylogeny constructed with a fragment of the heat shock (groEL) gene nucleotide sequences, all the identified A. phagocytophilum clustered with bacteria infecting a wide range of hosts, including humans, showing a potential zoonotic role.


Assuntos
Anaplasma phagocytophilum/isolamento & purificação , Doenças do Gato/microbiologia , Ehrlichiose/veterinária , Cabelo/microbiologia , Baço/microbiologia , Doenças Transmitidas por Vetores/veterinária , Anaplasma phagocytophilum/imunologia , Animais , Anticorpos Antibacterianos/sangue , Gatos , DNA Bacteriano/isolamento & purificação , Feminino , Masculino , Técnicas de Diagnóstico Molecular/veterinária , Doenças Transmitidas por Vetores/diagnóstico , Doenças Transmitidas por Vetores/microbiologia
7.
Biochim Biophys Acta Gen Subj ; 1865(1): 129760, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035602

RESUMO

BACKGROUND: Cancer cells show highly increased glucose utilization which, among other cancer-essential functions, was found to facilitate DNA repair. Lactate dehydrogenase (LDH) activity is pivotal for supporting the high glycolytic flux of cancer cells; to our knowledge, a direct contribution of this enzyme in the control of DNA integrity was never investigated. In this paper, we looked into a possible LDH-mediated regulation of homologous recombination (HR) repair. METHODS: We identified two cancer cell lines with different assets in energy metabolism: either based on glycolytic ATP or on oxidative reactions. In cells with inhibited LDH, we assessed HR function by applying four different procedures. RESULTS: Our findings revealed an LDH-mediated control of HR, which was observed independently of cell metabolic asset. Since HR inhibition is known to make cancer cells responsive to PARP inhibitors, in both the cellular models we finally explored the effects of a combined inhibition of LDH and PARP. CONCLUSIONS: The obtained results suggest for LDH a central role in cancer cell biology, not merely linked to the control of energy metabolism. The involvement of LDH in the DNA damage response could suggest new drug combinations to obtain improved antineoplastic effects. GENERAL SIGNIFICANCE: Several evidences have correlated the metabolic features of cancer cells with drug resistance and LDH inhibition has been repeatedly shown to increase the antineoplastic power of chemotherapeutics. By shedding light on the processes linking cell metabolism to the control of DNA integrity, our findings also give a mechanistic explanation to these data.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , L-Lactato Desidrogenase/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Ftalazinas/farmacologia , Piperazinas/farmacologia , Reparo de DNA por Recombinação/efeitos dos fármacos , Linhagem Celular Tumoral , Glicólise/efeitos dos fármacos , Humanos , L-Lactato Desidrogenase/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia
8.
Transbound Emerg Dis ; 68(3): 1283-1293, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32786111

RESUMO

Canine circovirus (CanineCV) is a relatively new viral species, belonging to the family Circoviridae, whose pathogenic role is still uncertain. Since its first description in one domestic dog in 2011 from the USA, several reports have been documenting its distribution worldwide. Recently, CanineCV was also detected in wild animals such as wolves, foxes and badgers. In order to investigate the presence and the genetic characteristics of CanineCV in foxes of Arctic and Sub-Arctic regions, the presence of CanineCV DNA in internal organs (liver and spleen) of 51 arctic foxes (Vulpes lagopus) from Svalbard archipelago and 59 red foxes (Vulpes vulpes) from Northern Norway, sampled from 1996 to 2001 and from 2014 to 2018, respectively, was screened by real-time PCR. CanineCV was detected in 11/51 arctic foxes and in 10/59 red foxes, backdating the circulation of the virus at least to 1996 in the arctic fox population. The complete genome of 14 identified CanineCV was sequenced and analysed showing an identity higher than 80.8% with the reference strains available to date. According to the species demarcation threshold of 80% genome-wide nucleotide sequence identity for members of the family Circoviridae provided by International Committee on Taxonomy of Viruses (ICTV), all the CanineCV belong to a single species. Phylogenetic analysis revealed that all the CanineCV were subdivided into five main clusters with one including only CanineCV identified in foxes. Furthermore, CanineCV identified in arctic foxes and red foxes formed two distinct lineages. From these data, we hypothesize that the viral transmission did not occur between the two species of foxes as a consequence of the lack of contact between the two hosts or that the virus acquired mutations in the time elapsed between the samplings.


Assuntos
Infecções por Circoviridae/veterinária , Circovirus/genética , Evolução Molecular , Raposas , Animais , Infecções por Circoviridae/virologia , Circovirus/classificação , Noruega , Filogenia , Análise de Sequência de DNA/veterinária , Especificidade da Espécie , Svalbard
9.
Front Vet Sci ; 7: 438, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32851021

RESUMO

A growing number of studies suggest that the lower urinary tract of humans and dogs can harbor a urinary microbiota. Nevertheless, a certain concern has developed that the microbiota reported could be due to unaccounted contamination, especially in low-biomass samples. The aim of this study was to investigate the bacterial community which populates the urine of healthy cats using two approaches: a culture-dependent approach which consisted of the expanded quantitative urine culture (EQUC) techniques capable of identifying live bacteria not growing in standard urine cultures, and a culture-independent approach which consisted of 16S ribosomal RNA next generation sequencing (16S rRNA NGS) capable of identifying bacterial DNA and exploring microbial diversity with high resolution. To avoid confounding factors of possible bacterial contamination, the urine was sampled using ultrasound-guided cystocentesis, and several sample controls and negative controls were analyzed. The urine sampled from the 10 cats included in the study showed no bacterial growth in the EQUC procedure. Although several reads were successfully originated using 16S rRNA NGS, a comparable pattern was observed between urine samples and the negative control, and no taxa were statistically accepted as non-contaminant. Taken together, the results obtained allowed stating that no viable bacteria were present in the urine of healthy cats without lower urinary tract disease and urinary tract infections, and that the bacterial DNA detected was of contaminant origin.

10.
Pathogens ; 9(5)2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32384672

RESUMO

Leptospirosis is an infectious disease that causes serious illness in dogs. For this reason, epidemiological and clinical studies focusing on disease characterization are widely advocated. The aim of this study was to characterize the leptospires identified in dogs with confirmed symptomatic acute leptospirosis. Leptospira spp. DNA detected in urine, blood, or both samples from nine infected dogs was analyzed using the multi-locus sequence typing (MLST) technique. Leptospires from two dogs were successfully typed: one was identified as belonging to Sequence Type (ST) 17 and one to ST198, both within the L. interrogans species, serogroups Icterohaemorrhagiae and Australis, respectively. Based on the results of routine serologic tests, antibodies reactive toward these serogroups are commonly revealed in dogs in Italy. This study provides the first molecular analysis that identifies infecting Leptospira directly on DNA from biological samples of dogs, showing that serogroup Australis can lead to a severe clinical presentation of leptospirosis in infected dogs.

11.
J Med Chem ; 63(5): 2588-2619, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32037829

RESUMO

Synthetic lethality is an innovative framework for discovering novel anticancer drug candidates. One example is the use of PARP inhibitors (PARPi) in oncology patients with BRCA mutations. Here, we exploit a new paradigm based on the possibility of triggering synthetic lethality using only small organic molecules (dubbed "fully small-molecule-induced synthetic lethality"). We exploited this paradigm to target pancreatic cancer, one of the major unmet needs in oncology. We discovered a dihydroquinolone pyrazoline-based molecule (35d) that disrupts the RAD51-BRCA2 protein-protein interaction, thus mimicking the effect of BRCA2 mutation. 35d inhibits the homologous recombination in a human pancreatic adenocarcinoma cell line. In addition, it synergizes with olaparib (a PARPi) to trigger synthetic lethality. This strategy aims to widen the use of PARPi in BRCA-competent and olaparib-resistant cancers, making fully small-molecule-induced synthetic lethality an innovative approach toward unmet oncological needs.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Proteína BRCA2/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Ftalazinas/farmacologia , Piperazinas/farmacologia , Rad51 Recombinase/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Antineoplásicos/química , Proteína BRCA2/genética , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Descoberta de Drogas , Sinergismo Farmacológico , Recombinação Homóloga/efeitos dos fármacos , Humanos , Modelos Moleculares , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Ftalazinas/química , Piperazinas/química , Inibidores de Poli(ADP-Ribose) Polimerases/química , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Mapas de Interação de Proteínas/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Mutações Sintéticas Letais/efeitos dos fármacos
12.
J Feline Med Surg ; 22(10): 935-943, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31957532

RESUMO

OBJECTIVES: The aims of this study were to investigate the prevalence of Leishmania species infection in cats in Northern Italy and to evaluate the associations between infection and signalment and clinicopathological data. METHODS: The study was carried out in a veterinary university hospital from June to November 2017. Blood, urine, conjunctival swabs and hair were collected from all randomly selected cats. Leishmania species infection was evaluated using the indirect fluorescent antibody test (IFAT), setting a cut-off value of 1:80, and using real-time PCR on blood, conjunctival and hair samples. A complete blood count, serum chemistry profile, serum electrophoresis and urinalysis were also carried out. The cats were grouped on the basis of the results of the diagnostic criteria adopted in positive, negative and unconfirmed Leishmania cases. Non-parametric variables and continuous data were compared among the study groups using the χ2 test and the Mann-Whitney U-test, respectively. RESULTS: One hundred and fifty-two cats were included. Nineteen of the 152 (12.5%) cats were positive (18/152 [11.8%] showed an IFAT titre of ⩾1:80 and 1/152 [0.7%] was real-time PCR-positive from a hair sample); 106/152 (69.7%) cats were negative; and 27/152 (17.8%) cats were unconfirmed for Leishmania species. Total proteins, beta2-globulin and gamma-globulin were significantly increased in the positive Leishmania group compared with the negative group. CONCLUSIONS AND RELEVANCE: The results of the present study demonstrated the spread of Leishmania infantum infection in cats in Northern Italy. Hyperproteinaemia and hypergammaglobulinaemia appeared to be significant clinicopathological abnormalities in this population of cats with L infantum infection.


Assuntos
Doenças do Gato/epidemiologia , Leishmania/isolamento & purificação , Leishmaniose/veterinária , Animais , Doenças do Gato/sangue , Doenças do Gato/parasitologia , Doenças do Gato/patologia , Gatos , Feminino , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Itália/epidemiologia , Leishmania infantum/isolamento & purificação , Leishmaniose/sangue , Leishmaniose/epidemiologia , Leishmaniose/parasitologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/veterinária , Masculino , Prevalência , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Estudos Soroepidemiológicos
13.
J Vet Intern Med ; 34(1): 176-185, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31705606

RESUMO

BACKGROUND: Urine neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury (AKI) in dogs. OBJECTIVES: To evaluate the utility of urinary NGAL for characterizing AKI according to volume responsiveness, presence of inflammation and sepsis, and prognosis. ANIMALS: Dogs with AKI (n = 76) and healthy controls (n = 10). METHODS: Prospective study. Clinical and clinicopathologic data including absolute urine NGAL concentration (uNGAL) and NGAL normalized to urine creatinine concentration (uNGALC) were measured upon admission. Dogs were graded according to International Renal Interest Society (IRIS) AKI guidelines and compared based on AKI features: volume-responsive (VR-) AKI vs. intrinsic (I-) AKI based on IRIS criteria; VR-AKI and I-AKI based on urine chemistry; inflammatory versus noninflammatory; septic versus nonseptic; and survivors versus nonsurvivors. Nonparametric statistics were calculated, and significance set at P < .05. RESULTS: Urinary NGAL was significantly higher in dogs with AKI compared to controls, regardless of AKI grade. Urinary NGAL did not differ between dogs with VR-AKI and I-AKI based on IRIS criteria, whereas higher uNGALC was recorded in dogs with I-AKI based on urine chemistry. Urinary NGAL was significantly higher in dogs with inflammatory AKI, whereas no difference with respect to sepsis or outcome was identified. CONCLUSIONS AND CLINICAL IMPORTANCE: Urinary NGAL is a sensitive marker for AKI in dogs, but its specificity is affected by systemic inflammation. Increased urinary NGAL in both I-AKI and VR-AKI also suggests the presence of tubular damage in transient AKI. Combining urine chemistry data with IRIS criteria could facilitate AKI characterization in dogs.


Assuntos
Doenças do Cão/diagnóstico , Nefropatias/veterinária , Lipocalina-2/urina , Animais , Biomarcadores , Estudos de Casos e Controles , Doenças do Cão/urina , Cães , Feminino , Nefropatias/urina , Masculino , Estudos Prospectivos
14.
J Wildl Dis ; 56(1): 239-242, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237820

RESUMO

Data on canine circovirus circulation among red foxes (Vulpes vulpes) are limited. We report the detection of canine circovirus in a red fox from Italy. The virus was closely related to strains from dogs (Canis lupus familiaris) rather than those from foxes, suggesting a possible transmission between the two species.


Assuntos
Infecções por Circoviridae/veterinária , Circovirus/genética , Raposas/virologia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Animais , Infecções por Circoviridae/epidemiologia , Infecções por Circoviridae/virologia , Circovirus/classificação , Genômica , Itália/epidemiologia , Filogenia
15.
BMC Vet Res ; 15(1): 393, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684949

RESUMO

BACKGROUND: Canine parvovirus type 2 (CPV-2) is the most important enteric virus infecting canids. It is a rapidly evolving virus; after its emergence in the 1970s, new antigenic variants (called CPV-2a, 2b and 2c) emerged and replaced the original antigenic type. The three antigenic variants are globally distributed with different frequencies and levels of genetic variability. This study focused on VP2 gene sequence analysis and the phylodynamics of CPV-2 which were detected in 123 dogs showing clinical signs of gastroenteritis collected in Italy from 1994 to 2017. RESULTS: For the most part, the sick dogs were young, and a third of them (32.5%) had been vaccinated. No statistical association was found between the CPV-2 antigenic variants, and sex, age, breed and vaccination status. Sequence analysis showed that all three antigenic types circulated in Italy; the CPV-2a type was the prominent genotype, followed by CPV-2c and CPV-2b, with notable differences regarding regional bases and significant fluctuations over time. Nucleotide sequence data showed high genetic heterogeneity with 67 nucleotide sequence types (ntSTs) identified, corresponding to 21 amino acid sequence types (aaSTs). The aaSTs and ntSTs obtained were distributed differently among the three CPV-2 antigenic variants: CPV-2a grouped 12/21 (57.1%) aaSTs and 41/67 (61.2%) ntSTs; CPV-2b grouped 5/21 (23.8%) aaSTs and 6/67 (8.9%) ntSTs, and CPV-2c grouped 4/21 (19.1%) aaSTs and 20/67 (29.9%) ntSTs. Canine parvovirus 2a was characterised by the highest genetic variability while CPV-2c was characterised by notable stability with a predominant amino acid profile during the entire sampling time. Canine parvovirus 2b re-emerged in recent years, showing a new and distinctive amino acid profile of the VP2 protein. CONCLUSIONS: The findings of the present study provided new insights regarding the phylodynamics and evolution of CPV-2 in Italy, pointing out notable differences at the local level in the distribution of the CPV-2 variants and the selection of genetic subtypes. The evolution of CPV-2 has raised questions regarding the efficacy of vaccination; therefore, continuous monitoring regarding the evolution and spread of new CPV-2 variants should be a key aim of ongoing research.


Assuntos
Doenças do Cão/virologia , Epidemiologia Molecular , Infecções por Parvoviridae/veterinária , Parvovirus Canino/genética , Animais , Doenças do Cão/epidemiologia , Cães , Variação Genética , Itália/epidemiologia , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/virologia , Parvovirus Canino/classificação , Filogenia
16.
J Wildl Dis ; 55(4): 935-939, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31166851

RESUMO

Canine adenovirus type 1 (CAdV-1) is the agent of infectious canine hepatitis, a severe frequently fatal disease affecting primarily dogs (Canis lupus familiaris). The virus has been detected in many wild carnivore species. Our aim was to evaluate the prevalence and genetic and histopathologic features of CAdV-1 in wild red foxes (Vulpes vulpes). Kidney and liver samples were obtained from 86 subjects, coming from the UK (n=21), Italy (n=36), and Germany (n=29). We used PCR, targeting the viral E3 gene and flanked regions, to detect the presence of the virus; viral E3, fiber, and E4 genes were sequenced and their sequences were compared with published sequences. Kidneys and liver from foxes in Italy and Great Britain (n=57) were prepared for histologic and immunohistochemical examination for CAdV-1. Viral DNA was detected in 22% (19 of 86) kidney samples, with E3 and E4 genes showing reported and unreported single nucleotide changes. No pathologic changes or viral immunopositive signals were detected in the examined tissues. Our study suggests that red foxes could be considered potential shedders of CAdV-1, as they showed a relatively high prevalence without related pathologic changes in the organs examined.


Assuntos
Infecções por Adenoviridae/veterinária , Adenovirus Caninos/isolamento & purificação , Raposas/virologia , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/virologia , Adenovirus Caninos/genética , Animais , Feminino , Alemanha/epidemiologia , Itália/epidemiologia , Rim/virologia , Fígado/virologia , Masculino , Reação em Cadeia da Polimerase/veterinária , Reino Unido/epidemiologia
17.
Vet Res Commun ; 43(2): 67-76, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30826932

RESUMO

Canine adenovirus type 1 (CAdV-1) is the aetiological agent of infectious canine hepatitis (ICH) in domestic dogs (Canis familiaris). In spite of the widespread use of vaccination, CAdV-1 continues to circulate in the dog population. Although a high number of serological screenings have indicated that CAdV-1 is widespread in fox species, little is known about the potential role of foxes as reservoirs of CAdV-1. Furthermore, very little data exist on the molecular features of this virus in foxes. To add to existing knowledge on CAdV-1 circulating in wild carnivores, tissue samples from CAdV-seropositive red foxes (Vulpes vulpes, n = 10) from the northern mainland of Norway and arctic foxes (Vulpes lagopus, n = 10) from the Svalbard archipelago, Norway, were investigated using a molecular approach to detect CAdV-1 DNA and important structural and non-structural genes of the detected viruses were sequenced and analysed. Amplicons characteristic for CAdV-1 were amplified from 14 out of 20 foxes (7 red foxes and 7 arctic foxes) and spleen and lymph node tissues resulted optimal targets for the viral DNA detection. The nucleotide sequences showed unique features that distinguished the viruses detected in this study from the CAdV-1 to date identified in wild carnivores and dogs. Greater attention should be given to genetically different CAdV-1 circulating in wild carnivores that may be transferred to dogs, potentially causing disease and reducing the effectiveness of available vaccines.


Assuntos
Infecções por Adenoviridae/virologia , Adenovirus Caninos/genética , Animais Selvagens/virologia , Raposas/virologia , Infecções por Adenoviridae/transmissão , Animais , DNA Viral/genética , Noruega , Svalbard
18.
J Wildl Dis ; 55(3): 737-741, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30789782

RESUMO

We report the detection of canine adenovirus type 1 DNA by real-time PCR technique in an oral sample of an Italian wolf (Canis lupus italicus). Genetic characterization of the virus revealed a strict relationship with viruses detected in dogs (Canis lupus familiaris), wolves, and red foxes (Vulpes vulpes), suggesting that transmission between wild animals and dogs had occurred.


Assuntos
Infecções por Adenoviridae/veterinária , Adenovirus Caninos/isolamento & purificação , Lobos/virologia , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/virologia , Adenovirus Caninos/genética , Animais , Itália/epidemiologia , Filogenia , Reação em Cadeia da Polimerase em Tempo Real/veterinária
19.
Eur J Med Chem ; 165: 80-92, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30660828

RESUMO

Olaparib is a PARP inhibitor (PARPi). For patients bearing BRCA1 or BRCA2 mutations, olaparib is approved to treat ovarian cancer and in clinical trials to treat breast and pancreatic cancers. In BRCA2-defective patients, PARPi inhibits DNA single-strand break repair, while BRCA2 mutations hamper double-strand break repair. Recently, we identified a series of triazole derivatives that mimic BRCA2 mutations by disrupting the Rad51-BRCA2 interaction and thus double-strand break repair. Here, we have computationally designed, synthesized, and tested over 40 novel derivatives. Additionally, we designed and conducted novel biological assays to characterize how they disrupt the Rad51-BRCA2 interaction and inhibit double-strand break repair. These compounds synergized with olaparib to target pancreatic cancer cells with functional BRCA2. This supports the idea that small organic molecules can mimic genetic mutations to improve the profile of anticancer drugs for precision medicine. Moreover, this paradigm could be exploited in other genetic pathways to discover innovative anticancer targets and drug candidates.


Assuntos
Antineoplásicos/química , Proteína BRCA2/metabolismo , Recombinação Homóloga/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Rad51 Recombinase/metabolismo , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Proteína BRCA2/genética , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Mimetismo Molecular , Mutação , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , Triazóis/síntese química
20.
Sci Rep ; 8(1): 15177, 2018 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-30310104

RESUMO

A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. In spite of intense study, it remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (-29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor. Cells from cotton rat, goat, and sheep provided control scenarios that represent host systems in which SARS-CoV is neither endemic nor epidemic. Independent of the cell system, the truncation of ORF8 (29 nt deletion) decreased replication up to 23-fold. The effect was independent of the type I interferon response. The 29 nt deletion in SARS-CoV is a deleterious mutation acquired along the initial human-to-human transmission chain. The resulting loss of fitness may be due to a founder effect, which has rarely been documented in processes of viral emergence. These results have important implications for the retrospective assessment of the threat posed by SARS.


Assuntos
Interações Hospedeiro-Patógeno , RNA Viral , Vírus da SARS/fisiologia , Deleção de Sequência , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/virologia , Replicação Viral/genética , Animais , Linhagem Celular , Células Cultivadas , Quirópteros/virologia , Reservatórios de Doenças , Humanos , Proteínas Recombinantes , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/metabolismo
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